A chemical small molecule induces mouse embryonic stem cell differentiation into functional vascular endothelial cells via Hmbox1

Stem Cells Dev. 2012 Oct 10;21(15):2762-9. doi: 10.1089/scd.2012.0055. Epub 2012 Jul 13.

Abstract

Embryonic stem cells (ESCs) can differentiate to endothelial progenitor cells and vascular endothelial cells (VECs), but the mechanism is largely unknown. In this study, we synthesized 2 chiral compounds (R-ABO and S-ABO) and identified R-ABO as an effective inducer of ESC differentiation into VECs. Furthermore, we found that R-ABO induced ESC differentiation into VECs via homeobox containing 1 (Hmbox1) that acted upstream of fibroblast growth factor 2 (FGF-2). The data suggest that R-ABO is a novel tool for ESC differentiation into VECs, and Hmbox1 is a key regulator in this differentiation process. These findings provide information on a novel target and a new platform for further investigating the gene control of ESC differentiation to VECs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Becaplermin
  • Benzoxazines / pharmacology*
  • Cell Culture Techniques
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / physiology*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology
  • Fibroblast Growth Factor 2 / metabolism
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Integrin beta4 / genetics
  • Integrin beta4 / metabolism
  • Mice
  • Mice, 129 Strain
  • Neovascularization, Physiologic
  • Proto-Oncogene Proteins c-sis / metabolism
  • Stereoisomerism
  • Transcriptional Activation
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine
  • Angiogenesis Inducing Agents
  • Benzoxazines
  • Hmbox1 protein, mouse
  • Homeodomain Proteins
  • Integrin beta4
  • Proto-Oncogene Proteins c-sis
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Fibroblast Growth Factor 2
  • Becaplermin